title: Clozapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation.
abstract: Clozapine (1-10 mg/kg s.c.) produces a selective increase in dopamine release in rat prefrontal cortex which is, in large part (approximately 50%), mediated via activation of 5-HT1A receptors. Clozapine is a moderately potent, partial 5-HT1A receptor agonist and activation of 5-HT1A receptors may contribute to its efficacy against negative symptoms and reduced extrapyramidal side effect liability. Agonist affinity for 5-HT1A receptors could thus be a desirable feature in the design of new antipsychotics.
authors.affiliation: Pfizer Inc., Department of Neuroscience, Groton, CT 06340, USA. hans_rollema@groton.pfizer.com
authors.forename: H
authors.initials: H
authors.lastname: Rollema
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: A W
authors.initials: AW
authors.lastname: Schmidt
authors.forename: S H
authors.initials: SH
authors.lastname: Zorn
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D014150:Antipsychotic Agents; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D003024:Clozapine; D004298:Dopamine